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Chapter 5b
Beyond the Semen Analysis

from the book How to Have a Baby: Overcoming Infertility
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.

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Blood Tests for Men

The serum FSH (follicle-stimulating hormone) level test is a very useful one for assessing testicular function. If the reason for the azoospermia or severe oligospermia is testicular failure, then this is reflected in a raised FSH level. This is because, in these patients, the testis also fails to produce a hormone called inhibin (which normally suppresses FSH levels to their normal range). A high FSH level is usually diagnostic of testicular failure. This test is done by a radioimmunoasay or ELISA test, and since it is a sophisticated test, it is best done in a specialized confirmation. The other reason for a high FSH level in some men is the consumption of clomiphene (a medicine often prescribed for the empiric treatment of oligospermia). This is why the test should be done only when no medication is being taken. While a high FSH level is diagnostic of testicular failure, a normal FSH level provides no useful information. A low FSH level is found in patients with hypogonadotropic hypogonadism. This is an LH (luteinizing hormone) level test, which provides mostly the same information.

A testosterone level test provides information on whether or not the testes are producing adequate amounts of the male hormone, namely, testosterone. Most infertile men have normal testosterone levels, because the compartment for testosterone production is separate from the compartment which produces sperm, and is usually intact in infertile men. A low testosterone level causes a decreased libido and this can be treated by testosterone or tablets). Of course, this therapy will not increase the sperm count.

In patients affected by azoospermia, there are basically only two reasons for the absence of sperm. One is because no sperm are being produced due to testicular failure. The other is that the sperm are being produced, but the outflow passage is blocked (ductal obstruction). The first test which needs to be done in these patients is an FSH level test. If this level is high, it means the problem is testicular failure. If, on the other hand, the FSH level is normal, then a testis biopsy is needed.

Ultrasound

An ultrasound of the testis has become a popular test to order, but its helpfulness is limited. The size of the testis is better assessed by clinical examination, using an orchidometer ; and while a Doppler ultrasound will often diagnose the presence of a varicocele, this is usually of little clinical significance . The danger of finding a varicocele is that the knee-jerk response is to do surgery to correct it – and this rarely benefits the patient. A transrectal ultrasound ( TRUS) can be useful, but only in evaluating selected patients with obstructive azoospermia, when a block at the level of the seminal vesicles is suspected, and this test is best ordered by a specialist.

Testicular Biopsy

A testicular biopsy is done in order to find out whether sperm production in the testis is normal or not. This is the "gold standard" for judging testicular function, since here the testicular tissue is being examined directly.

How is a testicular biopsy performed? This is a simple surgical procedure, which can be done under a local anesthetic, in the operation theatre or even in the doctor’s clinic, if it is well equipped. The test takes about 5-10 minutes to be carried out; and a biopsy could be taken from just one testis, or from both testes, depending upon the nature of the problem.

The removed bit of tissue is then placed in a special preservative fluid, which is then sent to a pathologist for examination under a microscope after staining.

The biopsy surgery doesn’t hurt, because the local anesthetic numbs the tissues. There may be dull ache for a few days after the procedure, but this can be relieved by mild analgesics.

Since testis biopsy is a surgical procedure, most doctors would use it as the last resort when testing the man. If you are advised to have a testis biopsy, ask the doctor how the result will change your treatment (a question you should ask before being subjected to any medical test, in fact !).

Formerly, when doctors performed a testis biopsy, they would send only one chunk of tissue for testing. However, today we know that a single biopsy may not be representative of the entire testis. Sperm production is not uniformly distributed throughout the testis, especially in men with testicular failure. This means that in order to get a true picture of sperm production in the testis, the doctor needs to sample at least 4 different areas of the testis, all of which need to be examined.

In the past, a testis biopsy was purely a diagnostic procedure. Today, it is also used to retrieve testicular sperm in order to treat men with severe male factor infertility. These testicular sperm can be used for intracytoplasmic sperm injection, or ICSI , a procedure described in detail in Chapter . Specialised infertility clinics also have the ability to freeze the testicular tissue. This testicular sperm freezing can be very useful, especially in men with small testes, as the biopsy does not need to be repeated again during treatment.

The interpretation: While the biopsy is an easy test to perform, it is difficult to interpret properly, unless done by an expert. The doctor looks for evidence of sperm production in the seminiferous tubules. In some cases, there is no sperm production at all (absent sperm- atogenesis); or the sperm production is arrested at a particular stage (maturation arrest). This implies testicular failure, which is usually irreversible, and there is no treatment for this malady. If, on the other hand, sperm production in the testes is completely normal, and yet there are no sperm in the ejaculated semen, this clearly means that there is a block in the male reproductive tract. This is the one condition in which a testis biopsy is extremely useful (i.e., in the evaluation of the azoospermic male, to determine if there is a block to sperm transport).

A testis biopsy is often a procedure which is done badly because it is so minor - so beware! It is preferable that the biopsy be done by a specialist; a poorly done biopsy may make reconstructive surgery on the epididymis more difficult later on, by causing adhesions and fibrosis (scarring). The commonest problem with the biopsy, however, is that the biopsy result is not reported accurately by the pathologist. Interpreting a testis biopsy is difficult and requires special expertise - and is not something that the ordinary pathologist does well. You should retrieve and retain your own slides and preserve them retrieve and retain your own slides and preserve them carefully. The pathology laboratory can also be instructed to keep the tissue ("blocks") carefully. It is unfortunately common to find that a testis biopsy has to be repeated simply because the first one was done so badly that its results could not be accurately interpreted. It may also be a good idea to get a second specialist’s opinion on the testis biopsy slides.

Vasography is another surgical test in which a radio-opaque dye is injected into the vas to determine if it is open, and, if blocked, to find out the exact site of the block. This test requires very delicated surgery and X-ray equipment and is a very infrequently done procedure because it can damage the vas.

For some men with testicular failure, a karyotype (study of the chromosomes) is useful, because it allows one to determine if a chromosomal problem (e.g., Klinefelter’s syndrome, 47, XXY, with an extra X Chromosome) is responsible for the azoospermia. Some research clinics also offer testing for microdeletions on the Y-chromosome – a newly discovered cause for testicular failure in about 15% of infertile men. While there is no treatment for this disorder, at least the test result provides an answer to the question of why the testes have failed- a question which, unfortunately, medicine today still cannot answer, in the majority of patients.

by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.

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